MP608 REAL-WORLD OUTCOMES OF MANAGEMENT WITH PATIROMER IN END-STAGE RENAL DISEASE PATIENTS UNDERGOING HEMODIALYSIS IN THE UNITED STATES Dinesh K. Chatoth, MD1, Peter M. Wahl, ScD2, Viatcheslav Rakov, MD3, Carly R. Van Zandt, MS4, Kathryn P. Anastassopoulos, MS2, Sam Colman, MSc2, Tyler Knight, MS2, Nina Oestreicher, PhD5, Ann Mooney, MSN4, David M. Spiegel, MD5 1Fresenius Medical Care North America, Waltham, MA, USA, 2Covance Market Access Inc., Gaithersburg, MD, USA, 3Vifor Pharma, Glattbrugg, Switzerland, 4Frenova Renal Research, Waltham, MA, USA, 5Relypsa Inc., a Vifor Pharma Company, Redwood City, CA, USA.

INTRODUCTION AND AIMS • Hyperkalemia (HK) is a life-threatening condition that is common in patients with end-stage renal disease (ESRD) and is associated with adverse clinical consequences. • Currently, there are a limited number of pharmaceutical products to treat and control HK. • Sodium (SPS) was the only available in the United States (US) until the US Food and Drug Administration approved patiromer in October 2015 for the treatment of HK.1 • The current version of the US Prescribing Information (November 2016)2 for patiromer reflects the most up-to-date pharmacovigilance information and supports the known safety profile of patiromer. • Use of SPS in daily practice is limited due to inferior tolerability and reported serious gastrointestinal events.3-7 • Clinical trials have demonstrated efficacy of patiromer,8,9 but little has been reported about patiromer in dialysis settings in clinical practice since it became commercially available in the US. • The aim of this study was to describe the real-world patient characteristics, management, and outcomes of patiromer for treatment of HK in patients undergoing hemodialysis (HD) for ESRD in a large US ESRD provider network. METHODS Study Design Analysis • Retrospective, descriptive cohort study of patients undergoing dialysis at Fresenius • Patient demographics and clinical characteristics were examined during the Care (FKC) centers using data from July 1, 2015, through October 31, 2016. pre-index period. • Patients were included in the study who met the following criteria: • Serum potassium (mEq/L) and potassium baths (1K) were examined during the – Initiated patiromer (first recorded prescription) between October 2015 and pre-index and post-index periods. July 2016. • Patiromer treatment patterns were examined during the post-index period: – Prescribed permanent, in-center HD at FKC prior to patiromer initiation. – Prescribed initiation dose – Prescribed HD ≥3 times per week. – Prescribed daily dose – ≥18 years of age. – Dose titrations up and down – ≥1 serum potassium (mEq/L; sK) laboratory value recorded in the 91 days prior to – Prescribed length of therapy patiromer initiation. • Pre-index sK was the last recorded value in the pre-index period. – No report of never filling the patiromer prescription. • Post-index sK were the last recorded values in the post-index time periods. Definitions – Week 1: 1-7 days (day 1 is index date) • The following definitions were used: – Week 2: 8-14 days – Index event: First recorded patiromer prescription at an FKC dialysis center. – Week 3: 15-21 days – Index date: The start date on the first recorded patiromer prescription. – Week 4: 22-28 days – Pre-index period: Up to the 91 days prior to the index date. – Month 2: 29-59 days – Post-index period: The period of continuous patiromer therapy including and – Month 3: 60-91 days following the index date, where continuous therapy ends at the earliest of the • Potassium baths were measured over the entire pre-index and post-index periods. following: patiromer stop date of last patiromer prescription, death date, FKC • Analyses were conducted for all patients and the following pre-index sK subgroups: discharge date, or 90 days after index date. If there is a gap between a patiromer prescription stop date and a following patiromer prescription start date, – sK ≤5.5 mEq/L continuous therapy will end with the prior patiromer prescription stop date. – sK >5.5 mEq/L – sK >6.5 mEq/L (subset of >5.5 mEq/L) • Analyses also examined patients who had a prescription for SPS during the pre-index period (SPS-switcher) and those who did not (SPS-naïve). RESULTS Patient Population Figure 2. Patiromer Prescribed Initiation Dose

• Among 317 patiromer initiators at FKC centers, 268 (84.5%) met the selection 8.4 g once a day 71.6% criteria (Figure 1). 8.4 g four times a week 10.4% • 89 patients (33.2%) switched from SPS to patiromer; 179 (66.8%) were naïve 8.4 g three times a week 4.5% to SPS. 8.4 g two times a week 3.0% Figure 1. Selection of Patient Population 16.8 g once a day 3.7% 8.4 g every other day 1.9% Initiated patiromer (first recorded prescription) between 8.4 g missing frequency 1.9% October 1, 2015 and October 31, 2016 (n=317) 8.4 g once a week 1.1% 16.8 g four times a week 0.8% Prescribed permanent, in-center HD at FKC prior to patiromer initiation 4.2 g once a day 0.4% (n=279) 16.8 g every other day 0.4% 8.4 g twice a day 0.4% Prescribed HD 3 times per week (n=275) Serum potassium pre- and post-index (Figure 3) Age ≥18 • Average sK was 5.8 mEq/L in the pre-index period. (n=274) • Overall, sK decreased 0.3 mEq/L by week 1 and remained decreased by ≥1 sK lab value recorded in the 91 days prior to patiromer initiation 0.4 mEq/L at month 2. (n=272) • Within the subgroups, sK decreased most among those with higher pre-index sK: No report of never filling patiromer prescription (n=268) – 5.5 mEq/L subgroup: no decrease – >5.5 mEq/L subgroup: 0.6 mEq/L by week 1 Pre-index sK ≤5.5 mEq/L Pre-index sK >5.5 mEq/L (n=89) (n=179) – >6.5 mEq/L subgroup: 1.3 mEq/L by week 1 • Results were similar for SPS-switcher and SPS-naïve patients. Pre-index sK >6.5 mEq/L (n=39) – SPS-switcher: sK decreased 0.3 mEq/L by week 1 FKC, Fresenius Kidney Care; HD, hemodialysis; sK, serum potassium. – SPS-naïve: sK decreased 0.4 mEq/L by week 1 Demographics and pre-index clinical characteristics (Table 1) Figure 3. Mean Serum Potassium (mEq/L) Before and After Patiromer Initiation • Mean age was 57.5 years. Overall ≤5.5 mEq/L >5.5 mEq/L >6.5 mEq/L • Over half were male (55.2%). 7.1 • Majority (77.2%) of patients were white. • Average body mass index was 27.4 kg/m2. 6.2 5.9 • Average time on dialysis was 4.9 years. 5.8 5.8 5.8 5.8 5.7 • The two most common causes of ESRD were type 2 diabetes (41.4%) and 5.7 5.6 hypertension (22.8%). 5.8 5.6 5.5 5.5 5.5 5.5 5.5 5.4 5.4 5.5 5.4 5.3 5.3 5.3 5.3 Table 1. Demographics and Pre-index Clinical Characteristics 5.1 5.1 4.9 Demographic/Clinical Characteristic N=268 Pre-index Week 1 Week 2 Week 3 Week 4 Month 2 Month 3 Age (years), mean (SD) 57.5 (13.1) Male, n (%) 148 (55.2) Potassium baths (1K) pre- and post-index Race, n (%) • The number of patients treated with at least one 1K bath decreased. White 207 (77.2) – Overall: 4.8% (31.7% to 26.9%) (Figure 4) Black 36 (13.4) – ≤5.5 mEq/L subgroup: 10.1% (29.2% to 19.1%) Other 25 (9.4) – >5.5 mEq/L subgroup: 2.3% (33.0% to 30.7%) Body mass index (kg/m2), mean (SD) 27.4 (6.5) – >6.5 mEq/L subgroup: 2.6% (46.2% to 43.6%) Time on dialysis (years), mean (SD) 4.9 (3.6) – SPS-switcher patients: 3.4% (23.6% to 20.2%) Potassium bath (1K) received, n (%) – SPS-naïve patients: 5.6% (35.8% to 30.2%) n (%) 85 (31.7) • Among patients who received 1K baths, the mean number of treatments using Mean number of 1K baths (SD) among those who received 16.4 (12.5) a 1K bath decreased. at least 1 – Overall: 1.7 (16.4 to 14.7) (Figure 4) ESRD cause, n (%), top 5 – ≤5.5 mEq/L subgroup: 4.4 (17.5 to 13.1) Type 2 diabetes mellitus 111 (41.4) – >5.5 mEq/L subgroup : 0.7 (15.9 to 15.2) Hypertension 61 (22.8) Nephritis 19 (7.1) – >6.5 mEq/L subgroup : 2.1 (15.7 to 13.6) Type 1 diabetes mellitus 18 (6.7) – SPS-switcher patients: 2.8 (18.4 to 15.6) Polycystic kidney disease 16 (6.0) – SPS-naïve patients: 1.4 (15.8 to 14.4) ESRD, end-stage renal disease; SD, standard deviation. Figure 4. Potassium Bath (1K) Utilization Before and After Patiromer Initiation % of Patients Average # of Baths (1K) 31.7 Patiromer treatment patterns 26.9 • The majority (71.6%) of patients initiated patiromer therapy on 8.4 g/day (Figure 2). • Another 21.3% of patients initiated patiromer therapy on <8.4 g/day (Figure 2),

resulting in a prescribed initiation average daily dose of 7.8 g/day. 16.4 • Few patients were titrated up (7.1%) or down (3.0%). 14.7 • Average daily dose during the post-index period was 7.9 g/day. • 201 patients (75.0%) had at least 91 days of continuous patiromer therapy. Pre-index Post-index CONCLUSIONS • These results from observational data on early adopters of patiromer in FKC dialysis centers in the US demonstrate that hyperkalemia management with patiromer lowers serum potassium in ESRD patients undergoing hemodialysis. • The greatest effect was observed among patients with severe hyperkalemia (pre-index sK >6.5 mEq/L) whose average daily patiromer dose was similar to that of less severe patients. • The occurrence and frequency of potassium baths (1K) decreased in this population after initiating patiromer for hyperkalemia treatment. • Results for SPS-naïve and SPS-switcher patients were similar for serum potassium but differences were observed in the need for 1K baths. • The predominant use of the recommended starting dose of 8.4 g/day as maintenance in this population supports the feasibility of this dose for long-term serum potassium control. References 1. US Department of Health and Human Services. US Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468546.htm. Updated October 22, 2015. Accessed November 10, 2016. 2. Relypsa Inc. (2016). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/205739s009lbl.pdf. Accessed April 24, 2017. 3. Palmer BF. N Engl J Med. 2004;351(6):585-592. 4. Harel Z, et al. Am J Med. 2013;126(3):264.e9-264.e24. 5. Nguyen T, et al. JAAPA. 2015;28(3):41-45. 6. Hagan AE, et al. Clin Nephrol. 2016;85(1):38-43. 7. Montaperto AG, et al. Curr Med Res Opin. 2016;32(1):155-164. 8. Bakris GL, et al; AMETHYST-DN Investigators. JAMA. 2015;314(2):151-161. 9. Weir MR, et al; OPAL-HK Investigators. N Engl J Med. 2015;372(3):211-221.

Presented at the 54th ERA–EDTA Congress, 3–6 June, 2017, Madrid, Spain. Supported by Relypsa, Inc., a Vifor Pharma Company FPO